Project Summary The purpose of this work is to develop a new class of gastric electrical stimulation (GES) therapies for the treatment of gastroparesis. Gastroparesis is a disorder arising from delayed gastric emptying leading to nausea, frequent vomiting, bloating, early satiety, and infection. Gastroparesis is common among diabetics and is a frequent side-effect of certain medications such as opiates. GES is believed to act by modulation of the stomach- brain axis. GES has been tested and approved as a treatment of gastroparesis, although there have been inconsistent reports of clinical efficacy. The mechanism of action of GES is not well understood and, as a result, parameters of GES are not standardized. This proposal will develop a new class of intragastric stimulators that can be delivered endoscopically, as opposed to current GES devices that are placed invasively. Furthermore, these devices will be used in conjunction with implanted brain electrodes in porcine models to directly examine the effect of gastric stimulation on various brain regions implicated in gastric motility and feeding. No previous study has conducted direct neural recording simultaneously with GES. This is a crucial step in characterizing the stomach-brain axis and vital to design more effective and less invasive GES therapies for patients with gastroparesis and other gastric disorders. The specific goals are summarized as follows: 1) Design and fabrication of endoscopically-delivered intragastric electrodes and 2) Characterization of GES effects on brain and gastric motility in large animal models. This proposal joins together fundamental engineering and tool development with a targeted clinical need, utilizing a wide-variety of disciplines in mechanical engineering, microfabrication, chemistry, biology, neuroscience, and gastroenterology.